The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–5, 2014 Copyright Ó 2014 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2014.09.008
Selected Topics: Neurological Emergencies
CEREBRAL VENOUS SINUS THROMBOPHLEBITIS AS A COMPLICATION OF ACUTE OTITIS MEDIA Kunal M. Sharma, MD* and James Ahn, MD† *Department of Emergency Medicine, University of Texas Health Science Center, Houston, Texas and †Section of Emergency Medicine, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois Reprint Address: Kunal M. Sharma, MD, Department of Emergency Medicine, University of Texas Health Science Center, 6431 Fannin Street, JJL 435, Houston, TX 77030
, Abstract—Background: While headache is a common emergency department chief complaint, cerebral venous sinus thrombosis (CVST) is an infrequently encountered cause of headache and is often not included in emergency physicians’ differential diagnoses for headache. Our objective is to review the latest data on epidemiology, presenting symptoms, diagnosis, and treatment of CVST. Case Report: A 27-year-old female presented to our emergency department with headache, blurred vision, and vomiting a day after being diagnosed with acute otitis media. Computed tomography scan of the brain without contrast in the emergency department was suggestive of CVST. Why Should an Emergency Physician Be Aware of This?: Although a rare cause of headache, CVST should be considered for a subset of patients presenting to the emergency department with the common complaint of headache. CVST is diagnosed by magnetic resonance venogram or computed tomography venogram of the brain. Anticoagulation with close monitoring in consultation with appropriate experts is a safe first-line therapy for CVST, even in patients with hemorrhage on initial imaging. Ó 2014 Elsevier Inc.
the emergency physician when evaluating a patient with headache. We present a case report of a young woman who presented with headache, nausea, vomiting, and blurred vision 1 day after being diagnosed with acute otitis media (OM). After presentation, she rapidly decompensated as a result of left transverse and sigmoid sinus thrombophlebitis with concomitant bacterial meningitis. Details of the patient’s clinical course, followed by a literature review regarding diagnosis and management of cerebral venous sinus thrombosis (CVST) and thrombophlebitis are detailed. CASE REPORT A 27-year-old female with no medical history presented to our ED with complaints of headache, left-sided monocular diplopia, and nausea. Although not taking oral contraceptives at the time of presentation, she reported recent intermittent use of oral contraceptives. She went to a local urgent care clinic and was diagnosed with acute left OM the day before presentation. After taking Augmentin and naproxen the morning of presentation, she noted a worsening headache prompting her to present to our ED. The patient’s initial triage vitals were temperature of 39 C, heart rate of 100 beats/min, respiratory rate of 16 breaths/min, room air saturation of 100%, and blood pressure of 140/80 mm Hg.
INTRODUCTION Management of patients with headache is common in the emergency department (ED). Although usually benign, the differential diagnosis for the headache ranges from benign to life threatening. The relative rarity of serious life threats manifested by headache further challenges
RECEIVED: 29 January 2013; FINAL SUBMISSION RECEIVED: 4 August 2014; ACCEPTED: 2 September 2014 1
2
Approximately 1 h after initial triage evaluation, the patient complained of a 10 out of 10 headache, along with dizziness and worsening left-eye double vision noted in all visual fields with both near and far gaze. She continued to be alert, oriented, and responding appropriately at this time. The patient was promptly evaluated by a senior emergency resident in triage. The resident noted pain behind her left ear and double vision of the left eye, along with a red and inflamed-appearing left tympanic membrane upon examination. The resident’s evaluation note expressed concern for mastoiditis or other intracranial processes. The patient’s triage priority was escalated and the patient was placed in a room shortly thereafter. In the meantime, laboratory studies and a noncontrast head computed tomography (CT) scan were ordered. Forty minutes later, the patient was noted to be slow to respond to verbal stimuli and was vomiting. Her Glasgow Coma Score was 9 (E: 2, V: 3, M: 4) with concern for further decline. She was intubated for airway protection and at this point, the treatment team was concerned for possible meningo-encephalitis. The patient was given intravenous anti-infective agents (i.e., ceftriaxone, vancomycin, ampicillin, and acyclovir) and steroids (1). A noncontrast head CT scan was notable for paucity of cortical sulci and fullness of basal cisterns concerning for cerebral edema; opacification of the left middle ear cavity compatible with OM; and increased attenuation within the left transverse sinus concerning for venous sinus thrombus (Figure 1) (2). The patient was admitted to the medical intensive care unit (ICU) with the neurologic intensive care team also following the patient. In the ICU, the patient was started on mannitol for concern for increased intracranial pressure from cerebral edema based on the head CT scan. A magnetic resonance image (MRI), including magnetic resonance angiogram (MRA) and magnetic resonance venogram (MRV), of the patient’s head were then obtained to further characterize the intracranial vasculature. The MRA was unremarkable. There were foci of abnormal signal in the distal left transverse sinus and proximal left sigmoid sinus on fluid attenuated inversion recovery images with the same defects noted on MRV as well, diagnostic of venous thromboses (Figure 2). There was no evidence of cerebral edema on MRI and mannitol was discontinued. The patient was subsequently started on therapeutic dosing of subcutaneous enoxaparin as a bridge to oral warfarin. On hospital day 2, the patient underwent left tympanostomy with noted purulent drainage, but without subsequent culture growth. She was extubated on hospital day 3 without difficulty and had no neurologic deficit, although her post-extubation course was notable for frequent complaint of headache.
K. M. Sharma and J. Ahn
Figure 1. Noncontrast head computed tomography showing increased attenuation in left transverse sinus (arrow) and fullness of basal cistern.
Her thrombophilia workup was negative. The infectious disease team believed that the patient had septic venous sinus thrombophlebitis and concomitant bacterial meningitis as a sequela of OM. She received 2 weeks of empiric
Figure 2. Brain magnetic resonance imaging fluid attenuated inversion recovery sequence showing abnormal signal in the proximal left sigmoid sinus (arrow).
Cerebral Venous Sinus Thrombophlebitis and Acute Otitis Media
antibiotic coverage for presumed bacterial meningitis and septic thrombophlebitis and was discharged with oral warfarin. She is doing well at the time of this writing. DISCUSSION In developed countries with ready access to antibiotics, CVST prevalence is quite low compared with both the pre-antibiotic era, where it often lead to significant morbidity and mortality, and with resource-poor countries where antibiotics are not readily obtained (3). Published data suggest that incidence of CVST is 1.32 per 100,000 person-years, significantly higher than previously suspected, and mortality at discharge and at follow-up is near 1% and 3%, respectively, both significantly decreased from prior estimations. These findings likely stem from more advanced and frequent imaging that allows the identification of less severe cases of CVST and the consequent discovery of a fairly indolent disease course for most cases of CVST (4). Predisposing risk factors for CVST include female sex (3:1 ratio), thrombophilia or other hematologic conditions, malignancy, underlying central nervous system disorders, vasculitides, pregnancy or puerperium, infection, drugs (including oral contraceptives, hormone replacement, and steroids), surgery, and dehydration (5). Cerebral venous sinus thrombophlebitis secondary to OM, as our patient had in our case presentation, is described in the literature (6). OM is one of the most frequently diagnosed conditions in EDs, particularly in the pediatric population (7). Treatment consists of expectant self-resolution or prescription of antibiotics. Overuse of antibiotics for treatment of OM is a well-documented phenomenon (7). In addition, antibiotic use in acute OM is controversial, with no evidence to substantiate that antibiotics prevent subsequent infections or hearing loss. Antibiotics are associated with reduced symptom duration and severity (number needed to treat = 8 and 21, respectively) but also with adverse events, most commonly antibiotic-associated diarrhea (number needed to harm = 11) (8). However, the literature is unclear on the role of antibiotics in preventing other potentially serious complications of OM, including CVST. Typical presenting symptoms of CVST can vary, although headache is most common and is present in up to 89% of patients presenting with CVST (9). Headache can range in intensity from ‘‘thunderclap’’ to subacute or chronic and progressive (9). Disturbances of consciousness or cognitive function consistent with an encephalopathic process may also be present. Focal signs and symptoms, including focal neurologic deficits and seizures, have been reported as presenting symptoms as well (10,11). On physical examination, headache may
3
worsen with Valsalva maneuvers. Papilledema may be present secondary to intracranial hypertension. Focal neurologic deficits or seizures are reported to be present in 40% of patients. Elderly patients are more likely to present with altered levels of consciousness when compared with younger patients (12). The pathophysiology of CVST is explained primarily by two phenomena. First, the venous thrombus leads to increased venous and capillary pressures secondary to blood flow limitation. As pressure rises, cerebral perfusion to the affected area is decreased, causing ischemic injury and cytotoxic edema, followed by disruption of the blood brain barrier and vasogenic edema. Capillary rupture can also occur causing parenchymal hemorrhage, explaining why a subset of patients present with hemorrhage as an initial finding on noncontrast head CT. Second, increased venous pressures secondary to flow limitation by the venous thrombus also prevent cerebrospinal fluid (CSF) reabsorption in the arachnoid granulations. This is especially true if there is significant clot burden in the superior sagittal sinus, where arachnoid granulations drain CSF. Decreased CSF reabsorption leads to increased CSF volume in the brain, which increases intracranial pressure, possibly worsening extant venular and capillary hypertension, causing edema and hemorrhage (12). Diagnosis of CVST most often begins with a noncontrast head CT to rule out hemorrhage. Although noncontrast head CT is not a sensitive study for CVST, several findings can suggest the presence of CVST. Radiographic evidence of CVST includes the following: a hyperdense ‘‘triangle sign,’’ a triangular or round-shaped hyperdensity in the posterior region of the superior sagittal sinus, on noncontrast head CT; an ‘‘empty delta’’ filling defect, a triangular pattern of contrast enhancement surrounded by a central region lacking enhancement in the posterior superior sagittal sinus, on contrast enhanced head CT; and the cord sign, a homogeneous, hyperattenuated appearance of thrombosed venous sinuses over the cerebral cortex usually seen on contrast-enhanced head CT (13,14). The gold standard for diagnosis today remains MRI and MRV. For patients who cannot undergo MRI or MRV, or for whom expeditious diagnosis is needed, CT venography (CTV) is both rapid and effective for diagnosis of CVST (12). Recent guidelines recommend imaging of the cerebral venous system if lobar intracranial hemorrhage of unclear etiology or cerebral infarction that does not conform to typical arterial boundaries is present (15). The utility of laboratory studies, specifically the Ddimer assay, in the diagnosis of CVST is questionable. One recent study reported that 4% of patients with CVST presenting with encephalopathy or papilledema had a negative D-dimer assay, defined as < 500 ng/mL.
4
Conversely, of patients with CVST presenting with isolated headache, 26% were found to have a D-dimer level < 500 ng/mL and 16% with a level of < 400 ng/mL. In total, 10% of patients with CVST had a negative D-dimer assay, raising doubt about the sensitivity of D-dimer to rule out CVST (16). According to recent guidelines, a negative D-dimer assay should not preclude further evaluation for CVST in the setting of high clinical suspicion (15). Lumbar puncture is useful if there is suspicion for meningitis, although elevated CSF cell counts should not sway one from pursuing a coexisting diagnosis of CVST if suspected (15). The mainstay of treatment for CVST is anticoagulation, even in patients with intracranial hemorrhage secondary to CVST noted on initial imaging (17). Meta-analysis data support the safety and efficacy of both unfractionated intravenous heparin and high-dose, body-weight adjusted, subcutaneous, low-molecular weight heparin (18). Notably, there were no conversions from ischemic infarcts to hemorrhagic infarcts in the two studies included in the meta-analysis mentioned previously. Despite these recommendations, variations in practice patterns exist, and consultation from experts in neurologic critical care, neurology, or neurosurgery is prudent. The remainder of inpatient management is focused on prevention or management of adverse sequelae, such as seizures or increased intracranial pressure, as well as search for an underlying cause of CVST (12). Thrombolysis or thrombectomy can be considered in those with worsening clinical course in the setting of optimized medical therapy, although this recommendation is only supported by case reports or small cases series (15). For cases in which thrombophlebitis is suspected, intravenous antibiotics should be administered promptly, even if lumbar puncture cannot be accomplished quickly (19). Based on historical data, common pathogens include Proteus species, Staphylococcus aureus (although rarely methicillin-resistant Staphylococcus), Escherichia coli, and anaerobic bacteria (19). As such, recommended antibiotics should include either a third- or fourth-generation cephalosporin and metronidazole. Patient’s diagnosed with CVST should be discharged with therapeutic anticoagulation, typically an oral agent such as warfarin (with a target international normalized ratio of 2 3) for 3 6 months for provoked CVST or 6 12 months for unprovoked CVST. Women who were previously on estrogen-based contraceptive therapies should seek non estrogen-based contraceptive methods. Finally, patients are recommended to undergo repeat imaging in 3 6 months to assess for recanalization, or sooner if symptoms do not resolve or worsen (12). Follow-up of discharged patients at 40 months from diagnosis showed that 89% of patients had complete re-
K. M. Sharma and J. Ahn
covery, 3.8% had partial recovery but were independent, and nearly 3% died. Only personal history of venous thromboembolism predicted future CVST events (20). Documented predictors of mortality included age, intracranial hemorrhage, hematologic disorders, systemic malignancy, and central nervous system infection (21). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? CVST is a more common entity than previously thought, with a generally more benign natural progression than previously understood. Emergency physicians should maintain CVST in their differential diagnoses in patients presenting with headache with concerning historical or examination features as described previously, as well as in those presenting with focal neurologic deficits. MRV remains the test of choice for diagnosing CVST, although CTV may be more rapidly available. Therapy consists of initial close monitoring, anticoagulation, and appropriate risk factor modification under the guidance of expert consultation. REFERENCES 1. de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347:1549–56. 2. Hasbun R, Abrahams J, Jekel J, Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med 2001;345:1727–33. 3. Fink JN, McAuley DL. Mastoid air sinus abnormalities associated with lateral venous sinus thrombosis: cause or consequence? Stroke 2002;33:290–2. 4. Coutinho JM, Zuurbier SM, Aramideh M, et al. The incidence of cerebral venous thrombosis: a cross-sectional study. Stroke 2012;43: 3375–7. 5. Ferro JM, Canhao P, Stam J, et al. Prognosis of cerebral vein and dural sinus thrombosis: results of the international study on cerebral vein and dural sinus thrombosis (ISCVT). Stroke 2004;35:664–70. 6. Seven H, Ozba AE, Turgut S. Management of otogenic lateral sinus thrombosis. Am J Otolaryngol 2004;25:329–33. 7. Bell LM. The new clinical practice guidelines for acute otitis media: an editorial. Ann Emerg Med 2005;45:514–6. 8. Worrall G. Acute otitis media. Can Fam Physician 2007;53:2147–8. 9. Cumurciuc R, Crassard I, Sarov M, Valade D, Bousser MG. Headache as the only neurological sign of cerebral venous thrombosis: a series of 17 cases. J Neurol Neurosurg Psychiatry 2005;76:1084–7. 10. Ferro JM, Canha˜o P, Stam J, Bousser MG, Barinagarrementeria F. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664–70. 11. Ferro JM, Canha˜o P, Bousser MG, Stam J, Barinagarrementeria F. Early seizures in cerebral vein and dural sinus thrombosis: risk factors and role of antiepileptics. Stroke 2008;39:1152–8. 12. Piazza G. Cerebral venous thrombosis. Circulation 2012;125: 1704–9. 13. Tang PH, Chai J, Chan YH, Chng SM, Lim CCT. Superior sagittal sinus thrombosis: subtle signs on neuroimaging. Ann Acad Med Singapore 2008;37:397–401. 14. Linn J, Pfefferkorn T, Ivanicova K, et al. Noncontrast CT in deep cerebral venous thrombosis and sinus thrombosis: comparison of its diagnostic value for both entities. Am J Neuroradiol 2009;30: 728–35.
Cerebral Venous Sinus Thrombophlebitis and Acute Otitis Media 15. Saposnik G, Barinagarrementeria F, Brown RD, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42: 1158–92. 16. Crassard I, Soria C, Tzourio C, et al. A negative d-dimer assay does not rule out cerebral venous thrombosis: a series of seventy-three patients. Stroke 2005;36:1716–9. 17. de Bruijn SF, Stam J. Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis. Stroke 1999;30:484–8.
5 18. Coutinho J, de Bruijn SFTM, deVeber G, et al. Anticoagulation for cerebral venous sinus thrombosis. Cochrane Database System Rev 2011;(8). 19. Southwick FS, Richardson EP Jr, Swartz MN. Septic thrombosis of the dural venous sinuses. Medicine (Baltimore) 1986;65:82. 20. Dentali F, Poli D, Scoditti U, et al. Long-term outcomes of patients with cerebral vein thrombosis: a multicenter study. J Thromb Haemost 2012;10:1297–302. 21. Haghighi AF, Edgell RC, Cruz-Flores S, et al. Mortality of central venous-sinus thrombosis in a large national sample. Stroke 2012; 43:262–4.
http://dx.doi.org/10.1016/j.jemermed.2014.09.008
Selected Topics: Neurological Emergencies
CEREBRAL VENOUS SINUS THROMBOPHLEBITIS AS A COMPLICATION OF ACUTE OTITIS MEDIA Kunal M. Sharma, MD* and James Ahn, MD† *Department of Emergency Medicine, University of Texas Health Science Center, Houston, Texas and †Section of Emergency Medicine, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois Reprint Address: Kunal M. Sharma, MD, Department of Emergency Medicine, University of Texas Health Science Center, 6431 Fannin Street, JJL 435, Houston, TX 77030
, Abstract—Background: While headache is a common emergency department chief complaint, cerebral venous sinus thrombosis (CVST) is an infrequently encountered cause of headache and is often not included in emergency physicians’ differential diagnoses for headache. Our objective is to review the latest data on epidemiology, presenting symptoms, diagnosis, and treatment of CVST. Case Report: A 27-year-old female presented to our emergency department with headache, blurred vision, and vomiting a day after being diagnosed with acute otitis media. Computed tomography scan of the brain without contrast in the emergency department was suggestive of CVST. Why Should an Emergency Physician Be Aware of This?: Although a rare cause of headache, CVST should be considered for a subset of patients presenting to the emergency department with the common complaint of headache. CVST is diagnosed by magnetic resonance venogram or computed tomography venogram of the brain. Anticoagulation with close monitoring in consultation with appropriate experts is a safe first-line therapy for CVST, even in patients with hemorrhage on initial imaging. Ó 2014 Elsevier Inc.
the emergency physician when evaluating a patient with headache. We present a case report of a young woman who presented with headache, nausea, vomiting, and blurred vision 1 day after being diagnosed with acute otitis media (OM). After presentation, she rapidly decompensated as a result of left transverse and sigmoid sinus thrombophlebitis with concomitant bacterial meningitis. Details of the patient’s clinical course, followed by a literature review regarding diagnosis and management of cerebral venous sinus thrombosis (CVST) and thrombophlebitis are detailed. CASE REPORT A 27-year-old female with no medical history presented to our ED with complaints of headache, left-sided monocular diplopia, and nausea. Although not taking oral contraceptives at the time of presentation, she reported recent intermittent use of oral contraceptives. She went to a local urgent care clinic and was diagnosed with acute left OM the day before presentation. After taking Augmentin and naproxen the morning of presentation, she noted a worsening headache prompting her to present to our ED. The patient’s initial triage vitals were temperature of 39 C, heart rate of 100 beats/min, respiratory rate of 16 breaths/min, room air saturation of 100%, and blood pressure of 140/80 mm Hg.
INTRODUCTION Management of patients with headache is common in the emergency department (ED). Although usually benign, the differential diagnosis for the headache ranges from benign to life threatening. The relative rarity of serious life threats manifested by headache further challenges
RECEIVED: 29 January 2013; FINAL SUBMISSION RECEIVED: 4 August 2014; ACCEPTED: 2 September 2014 1
2
Approximately 1 h after initial triage evaluation, the patient complained of a 10 out of 10 headache, along with dizziness and worsening left-eye double vision noted in all visual fields with both near and far gaze. She continued to be alert, oriented, and responding appropriately at this time. The patient was promptly evaluated by a senior emergency resident in triage. The resident noted pain behind her left ear and double vision of the left eye, along with a red and inflamed-appearing left tympanic membrane upon examination. The resident’s evaluation note expressed concern for mastoiditis or other intracranial processes. The patient’s triage priority was escalated and the patient was placed in a room shortly thereafter. In the meantime, laboratory studies and a noncontrast head computed tomography (CT) scan were ordered. Forty minutes later, the patient was noted to be slow to respond to verbal stimuli and was vomiting. Her Glasgow Coma Score was 9 (E: 2, V: 3, M: 4) with concern for further decline. She was intubated for airway protection and at this point, the treatment team was concerned for possible meningo-encephalitis. The patient was given intravenous anti-infective agents (i.e., ceftriaxone, vancomycin, ampicillin, and acyclovir) and steroids (1). A noncontrast head CT scan was notable for paucity of cortical sulci and fullness of basal cisterns concerning for cerebral edema; opacification of the left middle ear cavity compatible with OM; and increased attenuation within the left transverse sinus concerning for venous sinus thrombus (Figure 1) (2). The patient was admitted to the medical intensive care unit (ICU) with the neurologic intensive care team also following the patient. In the ICU, the patient was started on mannitol for concern for increased intracranial pressure from cerebral edema based on the head CT scan. A magnetic resonance image (MRI), including magnetic resonance angiogram (MRA) and magnetic resonance venogram (MRV), of the patient’s head were then obtained to further characterize the intracranial vasculature. The MRA was unremarkable. There were foci of abnormal signal in the distal left transverse sinus and proximal left sigmoid sinus on fluid attenuated inversion recovery images with the same defects noted on MRV as well, diagnostic of venous thromboses (Figure 2). There was no evidence of cerebral edema on MRI and mannitol was discontinued. The patient was subsequently started on therapeutic dosing of subcutaneous enoxaparin as a bridge to oral warfarin. On hospital day 2, the patient underwent left tympanostomy with noted purulent drainage, but without subsequent culture growth. She was extubated on hospital day 3 without difficulty and had no neurologic deficit, although her post-extubation course was notable for frequent complaint of headache.
K. M. Sharma and J. Ahn
Figure 1. Noncontrast head computed tomography showing increased attenuation in left transverse sinus (arrow) and fullness of basal cistern.
Her thrombophilia workup was negative. The infectious disease team believed that the patient had septic venous sinus thrombophlebitis and concomitant bacterial meningitis as a sequela of OM. She received 2 weeks of empiric
Figure 2. Brain magnetic resonance imaging fluid attenuated inversion recovery sequence showing abnormal signal in the proximal left sigmoid sinus (arrow).
Cerebral Venous Sinus Thrombophlebitis and Acute Otitis Media
antibiotic coverage for presumed bacterial meningitis and septic thrombophlebitis and was discharged with oral warfarin. She is doing well at the time of this writing. DISCUSSION In developed countries with ready access to antibiotics, CVST prevalence is quite low compared with both the pre-antibiotic era, where it often lead to significant morbidity and mortality, and with resource-poor countries where antibiotics are not readily obtained (3). Published data suggest that incidence of CVST is 1.32 per 100,000 person-years, significantly higher than previously suspected, and mortality at discharge and at follow-up is near 1% and 3%, respectively, both significantly decreased from prior estimations. These findings likely stem from more advanced and frequent imaging that allows the identification of less severe cases of CVST and the consequent discovery of a fairly indolent disease course for most cases of CVST (4). Predisposing risk factors for CVST include female sex (3:1 ratio), thrombophilia or other hematologic conditions, malignancy, underlying central nervous system disorders, vasculitides, pregnancy or puerperium, infection, drugs (including oral contraceptives, hormone replacement, and steroids), surgery, and dehydration (5). Cerebral venous sinus thrombophlebitis secondary to OM, as our patient had in our case presentation, is described in the literature (6). OM is one of the most frequently diagnosed conditions in EDs, particularly in the pediatric population (7). Treatment consists of expectant self-resolution or prescription of antibiotics. Overuse of antibiotics for treatment of OM is a well-documented phenomenon (7). In addition, antibiotic use in acute OM is controversial, with no evidence to substantiate that antibiotics prevent subsequent infections or hearing loss. Antibiotics are associated with reduced symptom duration and severity (number needed to treat = 8 and 21, respectively) but also with adverse events, most commonly antibiotic-associated diarrhea (number needed to harm = 11) (8). However, the literature is unclear on the role of antibiotics in preventing other potentially serious complications of OM, including CVST. Typical presenting symptoms of CVST can vary, although headache is most common and is present in up to 89% of patients presenting with CVST (9). Headache can range in intensity from ‘‘thunderclap’’ to subacute or chronic and progressive (9). Disturbances of consciousness or cognitive function consistent with an encephalopathic process may also be present. Focal signs and symptoms, including focal neurologic deficits and seizures, have been reported as presenting symptoms as well (10,11). On physical examination, headache may
3
worsen with Valsalva maneuvers. Papilledema may be present secondary to intracranial hypertension. Focal neurologic deficits or seizures are reported to be present in 40% of patients. Elderly patients are more likely to present with altered levels of consciousness when compared with younger patients (12). The pathophysiology of CVST is explained primarily by two phenomena. First, the venous thrombus leads to increased venous and capillary pressures secondary to blood flow limitation. As pressure rises, cerebral perfusion to the affected area is decreased, causing ischemic injury and cytotoxic edema, followed by disruption of the blood brain barrier and vasogenic edema. Capillary rupture can also occur causing parenchymal hemorrhage, explaining why a subset of patients present with hemorrhage as an initial finding on noncontrast head CT. Second, increased venous pressures secondary to flow limitation by the venous thrombus also prevent cerebrospinal fluid (CSF) reabsorption in the arachnoid granulations. This is especially true if there is significant clot burden in the superior sagittal sinus, where arachnoid granulations drain CSF. Decreased CSF reabsorption leads to increased CSF volume in the brain, which increases intracranial pressure, possibly worsening extant venular and capillary hypertension, causing edema and hemorrhage (12). Diagnosis of CVST most often begins with a noncontrast head CT to rule out hemorrhage. Although noncontrast head CT is not a sensitive study for CVST, several findings can suggest the presence of CVST. Radiographic evidence of CVST includes the following: a hyperdense ‘‘triangle sign,’’ a triangular or round-shaped hyperdensity in the posterior region of the superior sagittal sinus, on noncontrast head CT; an ‘‘empty delta’’ filling defect, a triangular pattern of contrast enhancement surrounded by a central region lacking enhancement in the posterior superior sagittal sinus, on contrast enhanced head CT; and the cord sign, a homogeneous, hyperattenuated appearance of thrombosed venous sinuses over the cerebral cortex usually seen on contrast-enhanced head CT (13,14). The gold standard for diagnosis today remains MRI and MRV. For patients who cannot undergo MRI or MRV, or for whom expeditious diagnosis is needed, CT venography (CTV) is both rapid and effective for diagnosis of CVST (12). Recent guidelines recommend imaging of the cerebral venous system if lobar intracranial hemorrhage of unclear etiology or cerebral infarction that does not conform to typical arterial boundaries is present (15). The utility of laboratory studies, specifically the Ddimer assay, in the diagnosis of CVST is questionable. One recent study reported that 4% of patients with CVST presenting with encephalopathy or papilledema had a negative D-dimer assay, defined as < 500 ng/mL.
4
Conversely, of patients with CVST presenting with isolated headache, 26% were found to have a D-dimer level < 500 ng/mL and 16% with a level of < 400 ng/mL. In total, 10% of patients with CVST had a negative D-dimer assay, raising doubt about the sensitivity of D-dimer to rule out CVST (16). According to recent guidelines, a negative D-dimer assay should not preclude further evaluation for CVST in the setting of high clinical suspicion (15). Lumbar puncture is useful if there is suspicion for meningitis, although elevated CSF cell counts should not sway one from pursuing a coexisting diagnosis of CVST if suspected (15). The mainstay of treatment for CVST is anticoagulation, even in patients with intracranial hemorrhage secondary to CVST noted on initial imaging (17). Meta-analysis data support the safety and efficacy of both unfractionated intravenous heparin and high-dose, body-weight adjusted, subcutaneous, low-molecular weight heparin (18). Notably, there were no conversions from ischemic infarcts to hemorrhagic infarcts in the two studies included in the meta-analysis mentioned previously. Despite these recommendations, variations in practice patterns exist, and consultation from experts in neurologic critical care, neurology, or neurosurgery is prudent. The remainder of inpatient management is focused on prevention or management of adverse sequelae, such as seizures or increased intracranial pressure, as well as search for an underlying cause of CVST (12). Thrombolysis or thrombectomy can be considered in those with worsening clinical course in the setting of optimized medical therapy, although this recommendation is only supported by case reports or small cases series (15). For cases in which thrombophlebitis is suspected, intravenous antibiotics should be administered promptly, even if lumbar puncture cannot be accomplished quickly (19). Based on historical data, common pathogens include Proteus species, Staphylococcus aureus (although rarely methicillin-resistant Staphylococcus), Escherichia coli, and anaerobic bacteria (19). As such, recommended antibiotics should include either a third- or fourth-generation cephalosporin and metronidazole. Patient’s diagnosed with CVST should be discharged with therapeutic anticoagulation, typically an oral agent such as warfarin (with a target international normalized ratio of 2 3) for 3 6 months for provoked CVST or 6 12 months for unprovoked CVST. Women who were previously on estrogen-based contraceptive therapies should seek non estrogen-based contraceptive methods. Finally, patients are recommended to undergo repeat imaging in 3 6 months to assess for recanalization, or sooner if symptoms do not resolve or worsen (12). Follow-up of discharged patients at 40 months from diagnosis showed that 89% of patients had complete re-
K. M. Sharma and J. Ahn
covery, 3.8% had partial recovery but were independent, and nearly 3% died. Only personal history of venous thromboembolism predicted future CVST events (20). Documented predictors of mortality included age, intracranial hemorrhage, hematologic disorders, systemic malignancy, and central nervous system infection (21). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? CVST is a more common entity than previously thought, with a generally more benign natural progression than previously understood. Emergency physicians should maintain CVST in their differential diagnoses in patients presenting with headache with concerning historical or examination features as described previously, as well as in those presenting with focal neurologic deficits. MRV remains the test of choice for diagnosing CVST, although CTV may be more rapidly available. Therapy consists of initial close monitoring, anticoagulation, and appropriate risk factor modification under the guidance of expert consultation. REFERENCES 1. de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002;347:1549–56. 2. Hasbun R, Abrahams J, Jekel J, Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med 2001;345:1727–33. 3. Fink JN, McAuley DL. Mastoid air sinus abnormalities associated with lateral venous sinus thrombosis: cause or consequence? Stroke 2002;33:290–2. 4. Coutinho JM, Zuurbier SM, Aramideh M, et al. The incidence of cerebral venous thrombosis: a cross-sectional study. Stroke 2012;43: 3375–7. 5. Ferro JM, Canhao P, Stam J, et al. Prognosis of cerebral vein and dural sinus thrombosis: results of the international study on cerebral vein and dural sinus thrombosis (ISCVT). Stroke 2004;35:664–70. 6. Seven H, Ozba AE, Turgut S. Management of otogenic lateral sinus thrombosis. Am J Otolaryngol 2004;25:329–33. 7. Bell LM. The new clinical practice guidelines for acute otitis media: an editorial. Ann Emerg Med 2005;45:514–6. 8. Worrall G. Acute otitis media. Can Fam Physician 2007;53:2147–8. 9. Cumurciuc R, Crassard I, Sarov M, Valade D, Bousser MG. Headache as the only neurological sign of cerebral venous thrombosis: a series of 17 cases. J Neurol Neurosurg Psychiatry 2005;76:1084–7. 10. Ferro JM, Canha˜o P, Stam J, Bousser MG, Barinagarrementeria F. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664–70. 11. Ferro JM, Canha˜o P, Bousser MG, Stam J, Barinagarrementeria F. Early seizures in cerebral vein and dural sinus thrombosis: risk factors and role of antiepileptics. Stroke 2008;39:1152–8. 12. Piazza G. Cerebral venous thrombosis. Circulation 2012;125: 1704–9. 13. Tang PH, Chai J, Chan YH, Chng SM, Lim CCT. Superior sagittal sinus thrombosis: subtle signs on neuroimaging. Ann Acad Med Singapore 2008;37:397–401. 14. Linn J, Pfefferkorn T, Ivanicova K, et al. Noncontrast CT in deep cerebral venous thrombosis and sinus thrombosis: comparison of its diagnostic value for both entities. Am J Neuroradiol 2009;30: 728–35.
Cerebral Venous Sinus Thrombophlebitis and Acute Otitis Media 15. Saposnik G, Barinagarrementeria F, Brown RD, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42: 1158–92. 16. Crassard I, Soria C, Tzourio C, et al. A negative d-dimer assay does not rule out cerebral venous thrombosis: a series of seventy-three patients. Stroke 2005;36:1716–9. 17. de Bruijn SF, Stam J. Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis. Stroke 1999;30:484–8.
5 18. Coutinho J, de Bruijn SFTM, deVeber G, et al. Anticoagulation for cerebral venous sinus thrombosis. Cochrane Database System Rev 2011;(8). 19. Southwick FS, Richardson EP Jr, Swartz MN. Septic thrombosis of the dural venous sinuses. Medicine (Baltimore) 1986;65:82. 20. Dentali F, Poli D, Scoditti U, et al. Long-term outcomes of patients with cerebral vein thrombosis: a multicenter study. J Thromb Haemost 2012;10:1297–302. 21. Haghighi AF, Edgell RC, Cruz-Flores S, et al. Mortality of central venous-sinus thrombosis in a large national sample. Stroke 2012; 43:262–4.
